Director-general Margaret Chan made the comments at the end of her two-day visit to Brazil, the country at the epicentre of the Zika crisis.
“Things may get worse before they get better,” Ms Chan said at a news conference in Rio de Janeiro. “Don’t be surprised to see microcephaly reported in other parts of Brazil.”
Ms Chan said part of the challenge is that the virus is so “mysterious”. Even the link to microcephaly remains not fully proven.
“We are dealing with a tricky virus, full of uncertainties, so we should be prepared for surprises,” she said.
As yet, Brazil’s zika outbreak has been concentrated in the northeastern part of the nation.
Much remains unknown about zika, including whether the virus actually causes microcephaly, a condition marked by unusually small heads that can result in developmental problems.
Ms Chan underscored that scientists are still working to determine causality between the virus and the birth defect.
Brazil said this week it has confirmed more than 580 cases of microcephaly, and considers most of them to be related to zika infections in the mothers.
Brazil is investigating more than 4,100 additional suspected cases of microcephaly.
After Brazil, Colombia has been hardest hit by zika infections, with the country’s health officials reporting a probable case of microcephaly possibly linked to zika in an aborted foetus.
Colombia has reported more than 37,000 cases of zika, including 6,356 in pregnant women, but it has yet to have a confirmed microcephaly case linked to the virus.
At least 34 countries, mostly in the Americas, have active zika outbreaks and the virus is expected to spread.
Florida said on Wednesday that three pregnant women who had travelled outside the US tested positive for the virus.
To protect their privacy, the state is not revealing the names or locations of the women.
The WHO declared the outbreak an international health emergency on February 1, citing a “strongly suspected” relationship between Zika infection in pregnancy and microcephaly.
Scientists are also studying a potential link between zika infection and Guillain-Barre, a rare neurological disorder that can weaken the muscles and cause paralysis.
Meanwhile the WHO says women in countries hit by the zika virus should breastfeed their babies and there is no proof the virus can spread to their infants that way.
In guidance, WHO said while zika has been detected in breast milk from two mothers sickened by the virus, there are no reports of zika being transmitted to babies via breastfeeding.
WHO said there have been no cases of babies suffering severe neurological problems or brain damage after being infected after birth.